199 research outputs found

    Deep Representation Learning with Limited Data for Biomedical Image Synthesis, Segmentation, and Detection

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    Biomedical imaging requires accurate expert annotation and interpretation that can aid medical staff and clinicians in automating differential diagnosis and solving underlying health conditions. With the advent of Deep learning, it has become a standard for reaching expert-level performance in non-invasive biomedical imaging tasks by training with large image datasets. However, with the need for large publicly available datasets, training a deep learning model to learn intrinsic representations becomes harder. Representation learning with limited data has introduced new learning techniques, such as Generative Adversarial Networks, Semi-supervised Learning, and Self-supervised Learning, that can be applied to various biomedical applications. For example, ophthalmologists use color funduscopy (CF) and fluorescein angiography (FA) to diagnose retinal degenerative diseases. However, fluorescein angiography requires injecting a dye, which can create adverse reactions in the patients. So, to alleviate this, a non-invasive technique needs to be developed that can translate fluorescein angiography from fundus images. Similarly, color funduscopy and optical coherence tomography (OCT) are also utilized to semantically segment the vasculature and fluid build-up in spatial and volumetric retinal imaging, which can help with the future prognosis of diseases. Although many automated techniques have been proposed for medical image segmentation, the main drawback is the model's precision in pixel-wise predictions. Another critical challenge in the biomedical imaging field is accurately segmenting and quantifying dynamic behaviors of calcium signals in cells. Calcium imaging is a widely utilized approach to studying subcellular calcium activity and cell function; however, large datasets have yielded a profound need for fast, accurate, and standardized analyses of calcium signals. For example, image sequences from calcium signals in colonic pacemaker cells ICC (Interstitial cells of Cajal) suffer from motion artifacts and high periodic and sensor noise, making it difficult to accurately segment and quantify calcium signal events. Moreover, it is time-consuming and tedious to annotate such a large volume of calcium image stacks or videos and extract their associated spatiotemporal maps. To address these problems, we propose various deep representation learning architectures that utilize limited labels and annotations to address the critical challenges in these biomedical applications. To this end, we detail our proposed semi-supervised, generative adversarial networks and transformer-based architectures for individual learning tasks such as retinal image-to-image translation, vessel and fluid segmentation from fundus and OCT images, breast micro-mass segmentation, and sub-cellular calcium events tracking from videos and spatiotemporal map quantification. We also illustrate two multi-modal multi-task learning frameworks with applications that can be extended to other domains of biomedical applications. The main idea is to incorporate each of these as individual modules to our proposed multi-modal frameworks to solve the existing challenges with 1) Fluorescein angiography synthesis, 2) Retinal vessel and fluid segmentation, 3) Breast micro-mass segmentation, and 4) Dynamic quantification of calcium imaging datasets

    Towards autonomous diagnostic systems with medical imaging

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    Democratizing access to high quality healthcare has highlighted the need for autonomous diagnostic systems that a non-expert can use. Remote communities, first responders and even deep space explorers will come to rely on medical imaging systems that will provide them with Point of Care diagnostic capabilities. This thesis introduces the building blocks that would enable the creation of such a system. Firstly, we present a case study in order to further motivate the need and requirements of autonomous diagnostic systems. This case study primarily concerns deep space exploration where astronauts cannot rely on communication with earth-bound doctors to help them through diagnosis, nor can they make the trip back to earth for treatment. Requirements and possible solutions about the major challenges faced with such an application are discussed. Moreover, this work describes how a system can explore its perceived environment by developing a Multi Agent Reinforcement Learning method that allows for implicit communication between the agents. Under this regime agents can share the knowledge that benefits them all in achieving their individual tasks. Furthermore, we explore how systems can understand the 3D properties of 2D depicted objects in a probabilistic way. In Part II, this work explores how to reason about the extracted information in a causally enabled manner. A critical view on the applications of causality in medical imaging, and its potential uses is provided. It is then narrowed down to estimating possible future outcomes and reasoning about counterfactual outcomes by embedding data on a pseudo-Riemannian manifold and constraining the latent space by using the relativistic concept of light cones. By formalizing an approach to estimating counterfactuals, a computationally lighter alternative to the abduction-action-prediction paradigm is presented through the introduction of Deep Twin Networks. Appropriate partial identifiability constraints for categorical variables are derived and the method is applied in a series of medical tasks involving structured data, images and videos. All methods are evaluated in a wide array of synthetic and real life tasks that showcase their abilities, often achieving state-of-the-art performance or matching the existing best performance while requiring a fraction of the computational cost.Open Acces

    3D exemplar-based image inpainting in electron microscopy

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    In electron microscopy (EM) a common problem is the non-availability of data, which causes artefacts in reconstructions. In this thesis the goal is to generate artificial data where missing in EM by using exemplar-based inpainting (EBI). We implement an accelerated 3D version tailored to applications in EM, which reduces reconstruction times from days to minutes. We develop intelligent sampling strategies to find optimal data as input for reconstruction methods. Further, we investigate approaches to reduce electron dose and acquisition time. Sparse sampling followed by inpainting is the most promising approach. As common evaluation measures may lead to misinterpretation of results in EM and falsify a subsequent analysis, we propose to use application driven metrics and demonstrate this in a segmentation task. A further application of our technique is the artificial generation of projections in tiltbased EM. EBI is used to generate missing projections, such that the full angular range is covered. Subsequent reconstructions are significantly enhanced in terms of resolution, which facilitates further analysis of samples. In conclusion, EBI proves promising when used as an additional data generation step to tackle the non-availability of data in EM, which is evaluated in selected applications. Enhancing adaptive sampling methods and refining EBI, especially considering the mutual influence, promotes higher throughput in EM using less electron dose while not lessening quality.Ein häufig vorkommendes Problem in der Elektronenmikroskopie (EM) ist die Nichtverfügbarkeit von Daten, was zu Artefakten in Rekonstruktionen führt. In dieser Arbeit ist es das Ziel fehlende Daten in der EM künstlich zu erzeugen, was durch Exemplar-basiertes Inpainting (EBI) realisiert wird. Wir implementieren eine auf EM zugeschnittene beschleunigte 3D Version, welche es ermöglicht, Rekonstruktionszeiten von Tagen auf Minuten zu reduzieren. Wir entwickeln intelligente Abtaststrategien, um optimale Datenpunkte für die Rekonstruktion zu erhalten. Ansätze zur Reduzierung von Elektronendosis und Aufnahmezeit werden untersucht. Unterabtastung gefolgt von Inpainting führt zu den besten Resultaten. Evaluationsmaße zur Beurteilung der Rekonstruktionsqualität helfen in der EM oft nicht und können zu falschen Schlüssen führen, weswegen anwendungsbasierte Metriken die bessere Wahl darstellen. Dies demonstrieren wir anhand eines Beispiels. Die künstliche Erzeugung von Projektionen in der neigungsbasierten Elektronentomographie ist eine weitere Anwendung. EBI wird verwendet um fehlende Projektionen zu generieren. Daraus resultierende Rekonstruktionen weisen eine deutlich erhöhte Auflösung auf. EBI ist ein vielversprechender Ansatz, um nicht verfügbare Daten in der EM zu generieren. Dies wird auf Basis verschiedener Anwendungen gezeigt und evaluiert. Adaptive Aufnahmestrategien und EBI können also zu einem höheren Durchsatz in der EM führen, ohne die Bildqualität merklich zu verschlechtern

    Analysis of tomographic images

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    Shape analysis of the human brain.

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    Autism is a complex developmental disability that has dramatically increased in prevalence, having a decisive impact on the health and behavior of children. Methods used to detect and recommend therapies have been much debated in the medical community because of the subjective nature of diagnosing autism. In order to provide an alternative method for understanding autism, the current work has developed a 3-dimensional state-of-the-art shape based analysis of the human brain to aid in creating more accurate diagnostic assessments and guided risk analyses for individuals with neurological conditions, such as autism. Methods: The aim of this work was to assess whether the shape of the human brain can be used as a reliable source of information for determining whether an individual will be diagnosed with autism. The study was conducted using multi-center databases of magnetic resonance images of the human brain. The subjects in the databases were analyzed using a series of algorithms consisting of bias correction, skull stripping, multi-label brain segmentation, 3-dimensional mesh construction, spherical harmonic decomposition, registration, and classification. The software algorithms were developed as an original contribution of this dissertation in collaboration with the BioImaging Laboratory at the University of Louisville Speed School of Engineering. The classification of each subject was used to construct diagnoses and therapeutic risk assessments for each patient. Results: A reliable metric for making neurological diagnoses and constructing therapeutic risk assessment for individuals has been identified. The metric was explored in populations of individuals having autism spectrum disorders, dyslexia, Alzheimers disease, and lung cancer. Conclusion: Currently, the clinical applicability and benefits of the proposed software approach are being discussed by the broader community of doctors, therapists, and parents for use in improving current methods by which autism spectrum disorders are diagnosed and understood

    Interactive Segmentation of 3D Medical Images with Implicit Surfaces

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    To cope with a variety of clinical applications, research in medical image processing has led to a large spectrum of segmentation techniques that extract anatomical structures from volumetric data acquired with 3D imaging modalities. Despite continuing advances in mathematical models for automatic segmentation, many medical practitioners still rely on 2D manual delineation, due to the lack of intuitive semi-automatic tools in 3D. In this thesis, we propose a methodology and associated numerical schemes enabling the development of 3D image segmentation tools that are reliable, fast and interactive. These properties are key factors for clinical acceptance. Our approach derives from the framework of variational methods: segmentation is obtained by solving an optimization problem that translates the expected properties of target objects in mathematical terms. Such variational methods involve three essential components that constitute our main research axes: an objective criterion, a shape representation and an optional set of constraints. As objective criterion, we propose a unified formulation that extends existing homogeneity measures in order to model the spatial variations of statistical properties that are frequently encountered in medical images, without compromising efficiency. Within this formulation, we explore several shape representations based on implicit surfaces with the objective to cover a broad range of typical anatomical structures. Firstly, to model tubular shapes in vascular imaging, we introduce convolution surfaces in the variational context of image segmentation. Secondly, compact shapes such as lesions are described with a new representation that generalizes Radial Basis Functions with non-Euclidean distances, which enables the design of basis functions that naturally align with salient image features. Finally, we estimate geometric non-rigid deformations of prior templates to recover structures that have a predictable shape such as whole organs. Interactivity is ensured by restricting admissible solutions with additional constraints. Translating user input into constraints on the sign of the implicit representation at prescribed points in the image leads us to consider inequality-constrained optimization

    Deep learning-based diagnostic system for malignant liver detection

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    Cancer is the second most common cause of death of human beings, whereas liver cancer is the fifth most common cause of mortality. The prevention of deadly diseases in living beings requires timely, independent, accurate, and robust detection of ailment by a computer-aided diagnostic (CAD) system. Executing such intelligent CAD requires some preliminary steps, including preprocessing, attribute analysis, and identification. In recent studies, conventional techniques have been used to develop computer-aided diagnosis algorithms. However, such traditional methods could immensely affect the structural properties of processed images with inconsistent performance due to variable shape and size of region-of-interest. Moreover, the unavailability of sufficient datasets makes the performance of the proposed methods doubtful for commercial use. To address these limitations, I propose novel methodologies in this dissertation. First, I modified a generative adversarial network to perform deblurring and contrast adjustment on computed tomography (CT) scans. Second, I designed a deep neural network with a novel loss function for fully automatic precise segmentation of liver and lesions from CT scans. Third, I developed a multi-modal deep neural network to integrate pathological data with imaging data to perform computer-aided diagnosis for malignant liver detection. The dissertation starts with background information that discusses the proposed study objectives and the workflow. Afterward, Chapter 2 reviews a general schematic for developing a computer-aided algorithm, including image acquisition techniques, preprocessing steps, feature extraction approaches, and machine learning-based prediction methods. The first study proposed in Chapter 3 discusses blurred images and their possible effects on classification. A novel multi-scale GAN network with residual image learning is proposed to deblur images. The second method in Chapter 4 addresses the issue of low-contrast CT scan images. A multi-level GAN is utilized to enhance images with well-contrast regions. Thus, the enhanced images improve the cancer diagnosis performance. Chapter 5 proposes a deep neural network for the segmentation of liver and lesions from abdominal CT scan images. A modified Unet with a novel loss function can precisely segment minute lesions. Similarly, Chapter 6 introduces a multi-modal approach for liver cancer variants diagnosis. The pathological data are integrated with CT scan images to diagnose liver cancer variants. In summary, this dissertation presents novel algorithms for preprocessing and disease detection. Furthermore, the comparative analysis validates the effectiveness of proposed methods in computer-aided diagnosis

    Revealing the Invisible: On the Extraction of Latent Information from Generalized Image Data

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    The desire to reveal the invisible in order to explain the world around us has been a source of impetus for technological and scientific progress throughout human history. Many of the phenomena that directly affect us cannot be sufficiently explained based on the observations using our primary senses alone. Often this is because their originating cause is either too small, too far away, or in other ways obstructed. To put it in other words: it is invisible to us. Without careful observation and experimentation, our models of the world remain inaccurate and research has to be conducted in order to improve our understanding of even the most basic effects. In this thesis, we1 are going to present our solutions to three challenging problems in visual computing, where a surprising amount of information is hidden in generalized image data and cannot easily be extracted by human observation or existing methods. We are able to extract the latent information using non-linear and discrete optimization methods based on physically motivated models and computer graphics methodology, such as ray tracing, real-time transient rendering, and image-based rendering
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